The rapidly changing epidemiology of type 2 diabetes and its frequent companion obesity, doubling in the last two decades, have disproportionately impacted Mexican Americans; a minority with already marked health disparity in these conditions owing to higher initial frequencies. Recognizing these disparities, the proposed Center of Excellence on Diabetes in Americans of Mexican Descent aims to conduct research on the physiologic progression to diabetes and its complications among Mexican Americans, and to develop diabetes prevention strategies and test innovative approaches to effective interventions in a minority population severely affected by type 2 diabetes. This Center proposes an administrative core, a research core including three research projects and two pilot studies, a training core and a community engagement core. The Center of Excellence Research Core is addressing this interaction in type 2 diabetes through three coordinated projects with the goal of understanding and implementing interventions to slow the current rate of increase in the disease and its complications. This is one of the three projects of the research core and will focus on the transitions in glucose status from normal to pre-diabetes to overt diabetes. In 2001, we initiated the establishment of the Cameron County Hispanic (Mexican American) Cohort as a complement to our two decades of work in Starr County, Texas. Prior to the start of this project we will have completed detailed physical evaluations on some 1,500 individuals living in Brownsville located the US/Mexico border. Our first aim is to document changes proximal to the development of overt diabetes. While metabolic and inflammatory risk factors are known to predict the development of type 2 diabetes in the long term, little is known regarding these profiles at the time of and immediately preceding the transition to overt disease. We will assess the impact of metabolic and inflammatory profiles and their regulation at the time of conversion and 3 and 6 months earlier by intensively following 300 individuals with pre-diabetes from our established cohort. The second aim is to determine the consequences of transitions in glucose status on the mental health of individuals with diabetes and its interaction with socioeconomic status. As with the onset of diabetes, inflammatory processes are also associated with deterioration in cognitive function. Further, stress and mental health can be affected by changes in glucose control. Currently, there are inadequate data in these regards for Hispanics, in general, and specifically for Hispanics with type 2 diabetes. Changes in mental health are likely slower to develop, but by examining the full Cameron County Hispanic Cohort we will determine the contribution of diabetes status to cognitive health